The USC Consortium (USCC) is a member of the Colon Cancer Family Registry (CFR). The USCC consists of the Universities of Arizona, Colorado, Dartmouth, Minnesota, North Carolina, and Southern California, which are the population-based centers in the consortium, and the Cleveland Clinic (CCF), which is our clinic-based center. We employed a multi-stage design to identify and recruit families. In the first phase, probands were screened for a family history of colorectal cancer (CRC). In the second phase, selected families were invited to join the CFR and provide core data items and biospecimens. Quite early, the USCC revised its specific aims in response to priorities established by the CFR. We decided to recruit 16 percent of single-case and 100 percent of multiple-case families into the CFR, and to focus our clinic-based recruitment on HNPCC and HNPCC-like families. Based on our revised design and the defined protocols of the CFR, we set goals of recruiting 634 population-based families and 150 clinic-based HNPCC or HNPCC-like families. We have made excellent progress in achieving our goals. As of November 1, we had signed informed consents from 627 population-based probands (about 99 percent of our target), and 116 HNPCC or HNPCC-like families. We have epidemiology questionnaires from 570 probands and 767 family members, and blood samples from 531 probands and 662 family members, and most centers project a retrieval rate of 90-100 percent for pathology reports and tumor blocks. The population-based centers will complete data collection by July, 2002, and CCF will extend data collection into the first year of the renewal. We have also made excellent progress in terms of research, with approved or ongoing projects involving LOI, methylation, a collaboration with GMP to assess the prevalence of missed MMR mutations by conventional genomic sequencing, proteomics, DNA repair, family history characteristics, screening for CRC, communication patterns in families, and statistical methodology. During the renewal period, our population-based centers will recruit 314 probands less than 50 and 1,012 family members, 384 African-American probands with 1,113 family members, and 75 Japanese American probands with 217 family members. The CCF will add an additional 20 high-risk families, with 200 family members. We will also conduct follow-up of an initial cohort of 3,152 CFR participants. The USC Genetic Epidemiology Lab will conduct methylation analyses of the MLH1 promoter for all centers in the CFR except Seattle.